From the Guidelines
Tardive dyskinesia is less common on clozapine compared to other antipsychotic medications.
Key Points
- The estimated risk of developing tardive dyskinesia on clozapine is around 1-5% after 1-2 years of treatment, and up to 10-15% after 5 years of treatment, with higher doses (above 400-500 mg/day) and longer treatment durations (above 2-3 years) increasing the risk 1.
- Risk factors for tardive dyskinesia include older age, female sex, and history of brain injury 1.
- Regular monitoring for signs of tardive dyskinesia is recommended for patients on clozapine, especially those with risk factors 1, 2.
- Clozapine is generally used only after a patient has either failed to respond to at least two therapeutic trials of other antipsychotic agents and/or developed significant side effects, including tardive dyskinesia 3, 4.
- The American Psychiatric Association recommends that patients with moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy be treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) 2.
From the Research
Prevalence of Tardive Dyskinesia Associated with Clozapine
- The prevalence of tardive dyskinesia associated with Clozapine is reported to be low, with studies suggesting a rate of approximately 1% compared to 5% for typical antipsychotics annually 5.
- A study published in 2009 found that the prevalence of tardive dyskinesia in patients taking Clozapine as a first-line antipsychotic drug was 3.96% (4/101) 6.
- Another study published in 1994 found that Clozapine produced a lower rate of oral dyskinesia in laboratory rats and significantly greater benefit for motor symptoms in patients with tardive dyskinesia compared to haloperidol 7.
- A study published in 1993 found that two patients in the Clozapine-treated group developed mild tardive dyskinesia, but the risk of tardive dyskinesia was likely to be less with Clozapine than with typical neuroleptics 8.
- A systematic review published in 2019 found that Clozapine reduces dyskinetic symptoms over time, but the minimum required dose and effect of withdrawal requires further investigation, and that Clozapine's liability for tardive dyskinesia is supported by case studies, but prospective randomized controlled trials are necessary to substantiate existing recommendations 9.
Comparison to Other Antipsychotics
- Atypical antipsychotics, including Clozapine, have a decreased liability of tardive dyskinesia compared to typical antipsychotics 5.
- No significant between-drug differences were identified comparing Clozapine's risk to other atypical antipsychotics 9.
Clinical Implications
- Regular examination for tardive dyskinesia using the activation procedure should be performed in patients who use Clozapine on a long-term basis 6.
- Switching to Clozapine may be recommended for the purpose of reducing tardive dyskinesia risk and/or treating existing tardive dyskinesia, but prospective randomized controlled trials are necessary to substantiate existing recommendations 9.